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At least 883 records · Page 49

Evaluation of Flow Biosensor Technology in a Chronically-Instrumented Non-Human Primate Model

The Physiology Research Branch of Brooks AFB conducts both human and non-human primate experiments to determine the effects of microgravity and hypergravity on the cardiovascular system and to indentify the particular mechanisms that invoke these responses. Primary investigative research efforts in a non-human primate model require the calculation of total peripheral resistance (TPR), systemic arterial compliance (SAC), and pressure-volume loop characteristics. These calculations require beat-to-beat measurement of aortic flow. We have evaluated commercially available electromagnetic (EMF) and transit-time flow measurement techniques. In vivo and in vitro experiments demonstrated that the average error of these techniques is less than 25 percent for EMF and less than 10 percent for transit-time.

SC Koenig↗

Closing the Loop on Space Trash / Is a Circular Economy Possible?

A crew member will nominally consume 2.5 kg of water per crew-member per day, rejectapproximately 0.032 kg of dry fecal solid waste per crew member per day (dry basis)and generate approximately 2,122 kg of logistical waste per year on a long-durationcrewed mission. This topic seeks to push the conversation towards completing a closedloop system and circular economy for all materials and recoverable resources withregard to waste management, regenerative water use, and recycling. In all aspects,reduction of crew maintenance time, mass, power and volume are at the forefront oftechnology development. In addition, the longevity and hardware robustness is important(lasting >3 years). Overall water recovery of >98% is desired, as well as, condensingheat exchangers that remove water from air with collection rates up to 1.45 kg of waterper hour. There are many technologies on the ground being developed for recycling andtrash management or regenerative water use that have yet to introduce themselves forspace development and infusion. Here we look to open the conversation and cross cutthese platforms to bring out some innovation and exposure into the hidden crevasses ofthe waste that humans create and how to minimize it/repurpose it, for all of humanity.

ISRU↗

A psychologist's view of validating aviation systems

All systems, no matter what they are designed to do, have shortcomings that may make them less productive than was hoped during the initial development. Such shortcomings can arise at any stage of development: from conception to the end of the implementation life cycle. While systems failure and errors of a lesser magnitude can occur as a function of mechanical or software breakdown, the majority of such problems, in aviation are usually laid on the shoulders of the human operator and, to a lesser extent, on human factors. The operator bears the responsibility and blame even though, from a human factors perspective, error may have been designed into the system. Human factors is not a new concept in aviation. The name may be new, but the issues related to operators in the loop date back to the industrial revolution of the nineteenth century and certainly to the aviation build-up for World War I. During this first global confrontation, military services from all sides discovered rather quickly that poor selection and training led to drastically increased personnel losses. While hardware design became an issue later, the early efforts were primarily focused on increased care in pilot selection and on their training. This actually involved early labor-intensive simulation, using such devices as sticks and chairs mounted on rope networks which could be manually moved in response to control input. The use of selection criteria and improved training led to more viable person-machine systems. More pilots survived training and their first ten missions in the air, a rule of thumb arrived at by experience which predicted ultimate survival better than any other. This rule was to hold through World War II. At that time, personnel selection and training became very sophisticated based on previous standards. Also, many psychologists were drafted into Army Air Corps programs which were geared towards refining the human factor. However, despite the talent involved in these programs and the tremendous build-up of aviation during the war, there were still aircraft designs that were man killers (no sexism implied since all combat pilots were men). One classic design error that was identified fifty years ago was the multipointer altimeter, which could easily be misread especially by a pilot under considerable task load. It has led to flying fully operational aircraft into the terrain. The authors of the research which formally identified this problem put 'Human Errors' in quotes to express their dissatisfaction with the traditional approach to accident investigation. It traditionally places the burden of guilt on the operator. Some of these altimeters still exist in older aircraft to this day.

Stein, Earl S.↗

Steady-state evoked potentials possibilities for mental-state estimation

The use of the human steady-state evoked potential (SSEP) as a possible measure of mental-state estimation is explored. A method for evoking a visual response to a sum-of-ten sine waves is presented. This approach provides simultaneous multiple frequency measurements of the human EEG to the evoking stimulus in terms of describing functions (gain and phase) and remnant spectra. Ways in which these quantities vary with the addition of performance tasks (manual tracking, grammatical reasoning, and decision making) are presented. Models of the describing function measures can be formulated using systems engineering technology. Relationships between model parameters and performance scores during manual tracking are discussed. Problems of unresponsiveness and lack of repeatability of subject responses are addressed in terms of a need for loop closure of the SSEP. A technique to achieve loop closure using a lock-in amplifier approach is presented. Results of a study designed to test the effectiveness of using feedback to consciously connect humans to their evoked response are presented. Findings indicate that conscious control of EEG is possible. Implications of these results in terms of secondary tasks for mental-state estimation and brain actuated control are addressed.

Junker, Andrew M.↗

A glycoprotein B-neutralizing antibody structure at 2.8 Å uncovers a critical domain for herpesvirus fusion initiation

Members of the Herpesviridae, including the medically important alphaherpesvirus varicella-zoster virus (VZV), induce fusion of the virion envelope with cell membranes during entry, and between cells to form polykaryocytes in infected tissues. The conserved glycoproteins, gB, gH and gL, are the core functional proteins of the herpesvirus fusion complex. gB serves as the primary fusogen via its fusion loops, but functions for the remaining gB domains remain unexplained. As a pathway for biological discovery of domain function, our approach used structure-based analysis of the viral fusogen together with a neutralizing antibody. We report here a 2.8 Å cryogenic-electron microscopy structure of native gB recovered from VZV-infected cells, in complex with a human monoclonal antibody, 93k. This high-resolution structure guided targeted mutagenesis at the gB-93k interface, providing compelling evidence that a domain spatially distant from the gB fusion loops is critical for herpesvirus fusion, revealing a potential new target for antiviral therapies. Herpesvirus virions have an outer lipid membrane dotted with glycoproteins that enable fusion with cell membranes to initiate entry and establish infection. Here the authors elucidate the structural mechanism of a neutralizing antibody derived from a patient infected by the herpesvirus varicella-zoster virus and targeted to its fusogen, glycoprotein-B.

59 BASIC BIOLOGICAL SCIENCES↗

Evaluation of Precision Landing Performance Using A Generalized Aerospace Simulation in Simulink Framework

NASA’s science and exploration goals to return to the Moon and beyond will need to perform precision landings to place humans and cargo supplies near places of scientific interest, surface resources, or pre-established basecamps. With the maturation of new navigation technology, such as terrain relative navigation, precision landing is now feasible, enabling new exploration sites, such as the lunar poles. However, verification of precision landing performance becomes crucial since not reaching the designated landing site would have a high risk of loss of mission. Therefore, having a high-fidelity simulation platform to evaluate six degrees of freedom vehicle performance during high-risk phases of flight such landing is a fundamental part of the system verification and risk reduction. The NASA Marshall Space Flight Center has developed the GeneraLized Aerospace Simulation in Simulink® (GLASS) tool which incorporates guidance, navigation, and control algorithms, as well as vehicle and environmental models, such as gravity, vehicle mass properties, navigation sensors, propulsion, and terrain models. GLASS uses the MathWorks® Simulink® environment which provides a model-based design framework that allows the incorporation of vehicle models in a modular architecture. The Simulink® environment provides seamless integration with all the MathWorks® capabilities and toolboxes, such as control design toolboxes and Simscape™ Multibody™ dynamics toolbox. The MathWorks® environment also allows for guidance, navigation, and control algorithms to be auto coded in C language, enabling quick software and hardware in the loop testing. This paper provides an overview of GLASS capabilities for analyzing precision landing performance, including navigation trades applied to a NASA human lander reference design architecture.

Guidance↗

From fault-detection to automated fault correction: A field study

A fault detection and diagnostics (FDD) tool, as addressed by this study, is a tool that continuously identifies the presence of faults and efficiency improvement opportunities through a one-way interface to the building automation system and the application of automated analytics. Although FDD tools can inform operators of building operational faults, currently an action is always required to correct the faults to generate energy savings. Fault auto-correction integrating with commercial FDD technology offerings can close the loop between the passive diagnostics and active control, increase the savings generated by FDD tools, and reduce the reliance on human intervention. This paper presents the field study of seven fault auto-correction algorithms implemented in commercial FDD platforms. Implementation includes software changes in the FDD tools and additional controls hardware or software changes in the BAS that were required to enable the execution of different types of auto-correction algorithms in real buildings. The routines successfully and automatically correct faults and improve the operation of large built-up Heating, Ventilation, and Air Conditioning (HVAC) systems, common in most commercial buildings. The auto-correction algorithms are tested across four buildings and three different building automation systems, following a rigorous procedure to make sure they work properly and do not negatively impact the system and building occupants. Finally, technology benefits, market drivers, and scalability changes are drawn from the implementation effort and test results, to drive future research and industry engagement.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗

A Multifaceted Approach to Modernizing NASA's Advanced Multi-Mission Operations System (AMMOS) System Architecture

The Advanced Multi-Mission Operations Systems (AMMOS) is NASA's premier space mission operations product line offering for use in deep-space robotic and astrophysics missions. The general approach to AMMOS modernization over the course of its 29-year history exemplifies a continual, evolutionary approach with periods of sponsor investment peaks and valleys in between. Today, the Multimission Ground Systems and Services (MGSS) office-the program office that manages the AMMOS for NASA-actively pursues modernization initiatives and continues to evolve the AMMOS by incorporating enhanced capabilities and newer technologies into its end-user tool and service offerings. Despite the myriad of modernization investments that have been made over the evolutionary course of the AMMOS, pain points remain. These pain points, based on interviews with numerous flight project mission operations personnel, can be classified principally into two major categories: 1) information-related issues, and 2) process-related issues. By information-related issues, we mean pain points associated with the management and flow of MOS data across the various system interfaces. By process-related issues, we mean pain points associated with the MOS activities performed by mission operators (i.e., humans) and supporting software infrastructure used in support of those activities. In this paper, three foundational concepts-Timeline, Closed Loop Control, and Separation of Concerns-collectively form the basis for expressing a set of core architectural tenets that provides a multifaceted approach to AMMOS system architecture modernization intended to address the information- and process-related issues. Each of these architectural tenets will be further explored in this paper. Ultimately, we envision the application of these core tenets resulting in a unified vision of a future-state architecture for the AMMOS-one that is intended to result in a highly adaptable, highly efficient, and highly cost-effective set of multimission MOS products and services.

Estefan, Jeff A.↗

EXTRACTING HUMAN RELIABILITY FINDINGS FROM HUMAN FACTORS STUDIES IN THE HUMAN SYSTEMS SIMULATION LABORATORY

Modernization of U.S. nuclear power plants (NPPs) is widespread, with most plants currently replacing and transitioning equipment, control systems, and human system interfaces (HSI)s from analog to digital displays. This conversion remedies the obsolescence of analog parts along with needs for increased intuitiveness of design, safety, and capabilities. The Human Factors and Reliability team at Idaho National Laboratory (INL) carried out twelve control room modernization studies in the newly designed Human Systems Simulation Laboratory (HSSL) over nine years. The HSSL was constructed as a testbed for evaluating human factors techniques and performance measures, HSI frameworks, and cutting-edge operational concepts in NPPs. Installing a full-scope training simulator enabled direct design and evaluation work on the same instrumentation and control (I&C) and HSIs located at U.S. plants. The subsequent addition of glass top bays afforded crews opportunities to implement operations via the simulator using full-scale representations of their home NPP. Additionally, functional HSI prototypes were created, providing an environment for operator-in-the-loop benchmark studies. The HSSL has assisted in upgrades of six commercial NPP control rooms and served as an invaluable proving ground for new NPP operations technology. Human reliability analysis (HRA) was not originally the focus of the studies; however, data relating to HRA such as type and frequency of human errors can be extracted from the studies. INL is currently extracting data from the HSSL study reports to apprise how information gathered from simulation, HSI, and other related studies can create a broad look across different data sources to help inform HRA methods.

99 GENERAL AND MISCELLANEOUS↗

Closed-loop Habitation Air Revitalization Model for Regenerative Life Support Systems

The primary function of any life support system is to keep the crew alive by providing breathable air, potable water, edible food, and for disposal of waste. In a well-balanced or regenerative life support system, the various components are each using what is available and producing what is needed by other components so that there will always be enough chemicals in the form in which they are needed. Humans are not just users, but also one of the participating parts of the system. If a system could continuously recycle the original chemicals, this would make it virtually a Closed-loop Habitation (CH). Some difficulties in trying to create a miniature version of a CH are briefly discussed. In a miniature CH, a minimal structure must be provided and the difference must be made up by artificial parts such as physicochemical systems that perform the conversions that the Earth can achieve naturally. To study the interactions of these parts, a computer model was designed that simulates a miniature CH with emphasis on the air revitalization part. It is called the Closed-loop Habitation Air Revitalization Model (CHARM).

Hart, Maxwell M.↗

Postural control model interpretation of stabilogram diffusion analysis

Collins and De Luca [Collins JJ. De Luca CJ (1993) Exp Brain Res 95: 308-318] introduced a new method known as stabilogram diffusion analysis that provides a quantitative statistical measure of the apparently random variations of center-of-pressure (COP) trajectories recorded during quiet upright stance in humans. This analysis generates a stabilogram diffusion function (SDF) that summarizes the mean square COP displacement as a function of the time interval between COP comparisons. SDFs have a characteristic two-part form that suggests the presence of two different control regimes: a short-term open-loop control behavior and a longer-term closed-loop behavior. This paper demonstrates that a very simple closed-loop control model of upright stance can generate realistic SDFs. The model consists of an inverted pendulum body with torque applied at the ankle joint. This torque includes a random disturbance torque and a control torque. The control torque is a function of the deviation (error signal) between the desired upright body position and the actual body position, and is generated in proportion to the error signal, the derivative of the error signal, and the integral of the error signal [i.e. a proportional, integral and derivative (PID) neural controller]. The control torque is applied with a time delay representing conduction, processing, and muscle activation delays. Variations in the PID parameters and the time delay generate variations in SDFs that mimic real experimental SDFs. This model analysis allows one to interpret experimentally observed changes in SDFs in terms of variations in neural controller and time delay parameters rather than in terms of open-loop versus closed-loop behavior.

NASA Program Biomedical Research and Countermeasur↗

A Structural Basis for Inhibition of the Complement Initiator Protease C1r by Lyme Disease Spirochetes

Abstract Complement evasion is a hallmark of extracellular microbial pathogens such as Borrelia burgdorferi, the causative agent of Lyme disease. Lyme disease spirochetes express nearly a dozen outer surface lipoproteins that bind complement components and interfere with their native activities. Among these, BBK32 is unique in its selective inhibition of the classical pathway. BBK32 blocks activation of this pathway by selectively binding and inhibiting the C1r serine protease of the first component of complement, C1. To understand the structural basis for BBK32-mediated C1r inhibition, we performed crystallography and size-exclusion chromatography–coupled small angle X-ray scattering experiments, which revealed a molecular model of BBK32-C in complex with activated human C1r. Structure-guided site-directed mutagenesis was combined with surface plasmon resonance binding experiments and assays of complement function to validate the predicted molecular interface. Analysis of the structures shows that BBK32 inhibits activated forms of C1r by occluding substrate interaction subsites (i.e., S1 and S1’) and reveals a surprising role for C1r B loop–interacting residues for full inhibitory activity of BBK32. The studies reported in this article provide for the first time (to our knowledge) a structural basis for classical pathway–specific inhibition by a human pathogen.

Garrigues, Ryan J. (ORCID:0000000259233250)↗

Automation effects in a multiloop manual control system

An experimental and analytical study was undertaken to investigate human interaction with a simple multiloop manual control system in which the human's activity was systematically varied by changing the level of automation. The system simulated was the longitudinal dynamics of a hovering helicopter. The automation-systems-stabilized vehicle responses from attitude to velocity to position and also provided for display automation in the form of a flight director. The control-loop structure resulting from the task definition can be considered a simple stereotype of a hierarchical control system. The experimental study was complemented by an analytical modeling effort which utilized simple crossover models of the human operator. It was shown that such models can be extended to the description of multiloop tasks involving preview and precognitive human operator behavior. The existence of time optimal manual control behavior was established for these tasks and the role which internal models may play in establishing human-machine performance was discussed.

Hess, R. A.↗

Analysis of Loss-of-Offsite-Power Events: Update

Loss-of-offsite power (LOOP) can have a negative impact on a nuclear power plant’s ability to achieve and maintain safe shutdown conditions. LOOP event frequencies and times required for subsequent restoration of offsite power are important inputs to plant probabilistic risk assessments. This report presents a statistical and engineering analysis of LOOP frequencies and durations at U.S. commercial nuclear power plants. The data used in this study were based on the operating experience during calendar years 1987–2020, while the most recent 15-year data (i.e., from 2006–2020) were used for most analyses in this report. LOOP events during critical operation that did not result in a reactor trip are not included. Frequencies and durations were determined for four LOOP event categories: plant-centered, switchyard-centered, grid-related, and weather related. Highly significant decreasing trends in the LOOP occurrence rates were identified for All-LOOPs during critical operation (p-value = 0.001) and switchyard-centered LOOPs during critical operation (p-value = 0.002) for the most recent 10-year period (2011–2020). Adverse trends in LOOP durations continue for switchyard-centered LOOPs (p-value = 0.005), All-LOOPs (p-value = 0.019), as well as All-LOOPs during shutdown operation (p-value = 0.003). Statistical tests show the LOOP counts are not uniformly distributed across the 12 months, and variation among the months exists for plant-centered LOOPs (p-value = 0.028), grid-related LOOPs (p-value = 0.021), All-LOOPs (p-value = 0.003), and All-LOOPs during critical operation (p-value = 0.008). The engineering analysis of LOOP data showed for the period of 2006–2020, the equipment failure events were dominated by failures of circuits and relay; human errors have been less frequent and occurred primarily in maintenance; and weather events were dominated by tornadoes and lightning.

22 GENERAL STUDIES OF NUCLEAR REACTORS↗

Correlated conformational dynamics of the human GluN1-GluN2A type N-methyl-D-aspartate (NMDA) receptor

N-Methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels found in the nerve cell membranes. As a result of overexcitation of NMDARs, neuronal death occurs and may lead to diseases such as epilepsy, stroke, Alzheimer’s disease, and Parkinson’s disease. In this study, human GluN1- GluN2A type NMDAR structure is modeled based on the X-ray structure of the Xenopus laevis template and missing loops are added by ab-initio loop modeling. The final structure is chosen according to two different model assessment scores. To be able to observe the structural changes upon ligand binding, glycine and glutamate molecules are docked into the corresponding binding sites of the receptor. Subsequently, molecular dynamics simulations of 1.3 μs are performed for both apo and ligand-bound structures. Structural parameters, which have been considered to show functionally important changes in previous NMDAR studies, are monitored as conformational rulers to understand the dynamics of the conformational changes. Moreover, principal component analysis (PCA) is performed for the equilibrated part of the simulations. Additionally, from these analyses, the differences in between apo and ligand-bound simulations can be summarized as the following: The girdle right at the beginning of the pore loop, which connects M2 and M3 helices of the ion channel, partially opens. Ligands act like an adhesive for the ligand-binding domain (LBD) by keeping the bi-lobed structure together and consequently this is reflected to the overall dynamics of the protein as an increased correlation of the LBD with especially the amino-terminal domain (ATD) of the protein.

59 BASIC BIOLOGICAL SCIENCES↗

Development and validation of a mathematical model of heart rate response to fluid perturbation

Physiological closed-loop controlled (PCLC) medical devices monitor and automatically adjust the patient’s condition by using physiological variables as feedback, ideally with minimal human intervention to achieve the target levels set by a clinician. PCLC devices present a challenge when it comes to evaluating their performance, where conducting large clinical trials can be expensive. Virtual physiological patients simulated by validated mathematical models can be utilized to obtain preclinical evidence of safety and assess the performance of the PCLC medical device during normal and worst-case conditions that are unlikely to happen in a limited clinical trial. A physiological variable that plays a major role during fluid resuscitation is heart rate (HR). For in silico assessment of PCLC medical devices regarding fluid perturbation, there is currently no mathematical model of HR validated in terms of its predictive capability performance. This paper develops and validates a mathematical model of HR response using data collected from sheep subjects undergoing hemorrhage and fluid infusion. The model proved to be accurate in estimating the HR response to fluid perturbation, where averaged between 21 calibration datasets, the fitting performance showed a normalized root mean square error (NRMSE) of 7.41 ± 2.8%. The model was also evaluated in terms of model predictive capability performance via a leave-one-out procedure (21 subjects) and an independent validation dataset (6 subjects). Two different virtual cohort generation tools were used in each validation analysis. The generated envelope of virtual subjects robustly met the defined acceptance criteria, in which 95% of the testing datasets presented simulated HR patterns that were within a deviation of 50% from the observed data. In addition, out of 16000 and 18522 simulated subjects for the leave one-out and independent datasets, the model was able to generate at least one virtual subject that was close to the real subject within an error margin of 9.56 ± 3.15% and 11.1 ± 1.22% NRMSE, respectively. In conclusion, the model can generate valid virtual HR physiological responses to fluid perturbation and be incorporated into future non-clinical simulated testing setups for assessing PCLC devices intended for fluid resuscitation.

59 BASIC BIOLOGICAL SCIENCES↗

Theoretical linear approach to the combined man-manipulator system in manual control of an aircraft

An approach to the calculation of the dynamic characteristics of the combined man manipulator system in manual aircraft control was derived from a model of the neuromuscular system. This model combines the neuromuscular properties of man with the physical properties of the manipulator system which is introduced as pilot manipulator model into the manual aircraft control. The assumption of man as a quasilinear and time invariant control operator adapted to operating states, depending on the flight phases, of the control system gives rise to interesting solutions of the frequency domain transfer functions of both the man manipulator system and the closed loop pilot aircraft control system. It is shown that it is necessary to introduce the complete precision pilot manipulator model into the closed loop pilot aircraft transfer function in order to understand the well known handling quality criteria, and to derive these criteria directly from human operator properties.

Brauser, K.↗